HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/5/C1281    most recent 00548.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Meyer, T. N. Articles by Denker, B. M. Search for Related Content PubMed PubMed Citation Articles by Meyer, T. N. Articles by Denker, B. M.

RECEPTORS AND SIGNAL TRANSDUCTION

G₁₂ regulates epithelial cell junctions through Src tyrosine kinases

¹Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and ²Division of Surgery, Children's Hospital, Boston, Massachusetts 02115

Submitted 25 November 2002 ; accepted in final form 8 July 2003

Regulation and assembly of the epithelial cell junctional complex involve multiple signaling mechanisms, including heterotrimeric G proteins. Recently, we demonstrated that G₁₂ binds to the tight junction scaffolding protein ZO-1 through the SH3 domain and that activated G₁₂ increases paracellular permeability in Madin-Darby canine kidney (MDCK) cells (Meyer et al. J Biol Chem 277: 24855-24858, 2002). In the present studies, we explore the effects of G₁₂ expression on tight and adherens junction proteins and examine downstream signaling pathways. By confocal microscopy, we detect disrupted tight and adherens junction proteins with increased actin stress fibers in constitutively active G₁₂ (QL₁₂)-expressing MDCK cells. The normal distribution of ZO-1 and Na-K-ATPase was altered in QL₁₂-expressing MDCK cells, consistent with loss of polarity. We found that the tyrosine kinase inhibitor genistein and the Src-specific inhibitor PP-2 reversibly abrogated the QL₁₂ phenotype on the junctional complex. Junctional protein localization was preserved in PP-2- or genistein-treated QL₁₂-expressing cells, and the increase in paracellular permeability as measured by transepithelial resistance and [³H]mannitol flux was prevented by the inhibitors. Src activity was increased in QL₁₂-expressing MDCK cells as assessed by Src autophosphorylation, and -catenin tyrosine phosphorylation was also increased, although there was no detectable increase in Rho activity. Taken together, these results indicate that G₁₂ regulates MDCK cell junctions, in part through Src tyrosine kinase pathways.

G proteins; tight junction; adherens junction; Rho

This article has been cited by other articles:

				T. Kong, D. Xu, W. Yu, A. Takakura, I. Boucher, M. Tran, J. A. Kreidberg, J. Shah, J. Zhou, and B. M. Denker G{alpha}12 Inhibits {alpha}2{beta}1 Integrin-mediated Madin-Darby Canine Kidney Cell Attachment and Migration on Collagen-I and Blocks Tubulogenesis Mol. Biol. Cell, November 1, 2009; 20(21): 4596 - 4610. [Abstract] [Full Text] [PDF]

				S.-C. Liu, Y.-M. Jen, S. S. Jiang, J.-L. Chang, C. A. Hsiung, C.-H. Wang, and J.-L. Juang G{alpha}12-Mediated Pathway Promotes Invasiveness of Nasopharyngeal Carcinoma by Modulating Actin Cytoskeleton Reorganization Cancer Res., August 1, 2009; 69(15): 6122 - 6130. [Abstract] [Full Text] [PDF]

				D. S. Charba, R. C. Wiggins, M. Goyal, B. L. Wharram, J. E. Wiggins, E. T. McCarthy, R. Sharma, M. Sharma, and V. J. Savin Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase glomerular albumin permeability (Palb) Am J Physiol Renal Physiol, July 1, 2009; 297(1): F138 - F144. [Abstract] [Full Text] [PDF]

				E. Sabath, H. Negoro, S. Beaudry, M. Paniagua, S. Angelow, J. Shah, N. Grammatikakis, A. S. L. Yu, and B. M. Denker G{alpha}12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly J. Cell Sci., March 15, 2008; 121(6): 814 - 824. [Abstract] [Full Text] [PDF]

				L. Song, S. Ge, and J. S. Pachter Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells Blood, February 15, 2007; 109(4): 1515 - 1523. [Abstract] [Full Text] [PDF]

				S. Kim, J. Jin, and S. P. Kunapuli Relative contribution of G-protein-coupled pathways to protease-activated receptor-mediated Akt phosphorylation in platelets Blood, February 1, 2006; 107(3): 947 - 954. [Abstract] [Full Text] [PDF]

				J. L. Hunt, M. R. Pollak, and B. M. Denker Cultured Podocytes Establish a Size-Selective Barrier Regulated by Specific Signaling Pathways and Demonstrate Synchronized Barrier Assembly in a Calcium Switch Model of Junction Formation J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1593 - 1602. [Abstract] [Full Text] [PDF]

				M. Boccellino, G. Camussi, A. Giovane, L. Ferro, V. Calderaro, C. Balestrieri, and L. Quagliuolo Platelet-Activating Factor Regulates Cadherin-Catenin Adhesion System Expression and {beta}-Catenin Phosphorylation during Kaposi's Sarcoma Cell Motility Am. J. Pathol., May 1, 2005; 166(5): 1515 - 1522. [Abstract] [Full Text] [PDF]